Home > Archive>Volume 52, Issue 1, 2025 >60-77. DOI:10.13344/j.microbiol.china.240308
PDF HTML XML Export Cite reminder
Current status and prospects of research on intratumoral microorganisms and progression of colorectal cancer
Author:
  • Article
    • | |
  • Metrics
    • |
  • Reference [95]
    • |
  • Related [20]
    • | | |
  • Comments
    Abstract:

    As one of the common and deadly malignant tumors worldwide, colorectal cancer (CRC) poses a serious threat to public health and causes a heavy burden to the society. The influences of microorganisms on the occurrence and development of CRC has received much attention from researchers, whereas most of the available studies have focused on gut microorganisms. In recent years, with the rapid development of next-generation sequencing, intratumoral microorganisms of CRC have been discovered and gradually opened up new research areas. We review the research progress in intratumoral microorganisms of CRC and their effects on the course of CRC and compare the relative abundance and community composition of intratumoral microorganisms of CRC with different molecular subtypes, at different stages of adenoma-carcinoma progression, and at different locations. Intratumoral microorganisms mainly affect CRC development by influencing colonic epithelial cells, tumor cells, and immune cells, with the pathogenic mechanisms including DNA damage, metabolic reprogramming, and oncogenic non-coding RNAs. Different intratumoral microorganisms exert dual effects on CRC. In the future, comprehensive experimental protocols and suitable in vitro models should be established to overcome the limitations of existing studies and elucidate the functioning mechanisms of intratumoral microorganisms, which will lay a foundation for the clinical application of microorganisms-targeted therapies for CRC and even other tumors.

    Reference
    [1] BRAY F, FERLAY J, SOERJOMATARAM I, SIEGEL RL, TORRE LA, JEMAL A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA: a Cancer Journal for Clinicians, 2018, 68(6): 394-424.
    [2] SPAANDER MCW, ZAUBER AG, SYNGAL S, BLASER MJ, SUNG JJ, YOU YN, KUIPERS EJ. Young-onset colorectal cancer[J]. Nature Reviews Disease Primers, 2023, 9: 21.
    [3] SONG MY, CHAN AT, SUN J. Influence of the gut microbiome, diet, and environment on risk of colorectal cancer[J]. Gastroenterology, 2020, 158(2): 322-340.
    [4] BERTOCCHI A, CARLONI S, RAVENDA PS, BERTALOT G, SPADONI I, CASCIO AL, GANDINI S, LIZIER M, BRAGA D, ASNICAR F, SEGATA N, KLAVER C, BRESCIA P, ROSSI E, ANSELMO A, GUGLIETTA S, MAROLI A, SPAGGIARI P, TARAZONA N, CERVANTES A, et al. Gut vascular barrier impairment leads to intestinal bacteria dissemination and colorectal cancer metastasis to liver[J]. Cancer Cell, 2021, 39(5): 708-724.e11.
    [5] NEJMAN D, LIVYATAN I, FUKS G, GAVERT N, ZWANG Y, GELLER LT, ROTTER-MASKOWITZ A, WEISER R, MALLEL G, GIGI E, MELTSER A, DOUGLAS GM, KAMER I, GOPALAKRISHNAN V, DADOSH T, LEVIN-ZAIDMAN S, AVNET S, ATLAN T, COOPER ZA, ARORA R, et al. The human tumor microbiome is composed of tumor type-specific intracellular bacteria[J]. Science, 2020, 368(6494): 973-980.
    [6] NARUNSKY-HAZIZA L, SEPICH-POORE GD, LIVYATAN I, ASRAF O, MARTINO C, NEJMAN D, GAVERT N, STAJICH JE, AMIT G, GONZÁLEZ A, WANDRO S, PERRY G, ARIEL R, MELTSER A, SHAFFER JP, ZHU QY, BALINT-LAHAT N, BARSHACK I, DADIANI M, GAL-YAM EN, et al. Pan-cancer analyses reveal cancer-type-specific fungal ecologies and bacteriome interactions[J]. Cell, 2022, 185(20): 3789-3806.e17.
    [7] DOHLMAN AB, KLUG J, MESKO M, GAO IH, LIPKIN SM, SHEN XL, ILIEV ID. A pan-cancer mycobiome analysis reveals fungal involvement in gastrointestinal and lung tumors[J]. Cell, 2022, 185(20): 3807-3822.e12.
    [8] GALEANO NIÑO JL, WU HR, LaCOURSE KD, KEMPCHINSKY AG, BARYIAMES A, BARBER B, FUTRAN N, HOULTON J, SATHER C, SICINSKA E, TAYLOR A, MINOT SS, JOHNSTON CD, BULLMAN S. Effect of the intratumoral microbiota on spatial and cellular heterogeneity in cancer[J]. Nature, 2022, 611: 810-817.
    [9] TJALSMA H, BOLEIJ A, MARCHESI JR, DUTILH BE. A bacterial driver-passenger model for colorectal cancer: beyond the usual suspects[J]. Nature Reviews Microbiology, 2012, 10: 575-582.
    [10] WANG YJ, WAN XH, WU XJ, ZHANG CZ, LIU J, HOU SB. Eubacterium rectale contributes to colorectal cancer initiation via promoting colitis[J]. Gut Pathogens, 2021, 13(1): 2.
    [11] BIEN J, PALAGANI V, BOZKO P. The intestinal microbiota dysbiosis and Clostridium difficile infection: is there a relationship with inflammatory bowel disease?[J]. Therapeutic Advances in Gastroenterology, 2013, 6(1): 53-68.
    [12] YU YN, FANG JY. Gut microbiota and colorectal cancer[J]. Gastrointestinal Tumors, 2015, 2(1): 26-32.
    [13] YOUNGINGER BS, MAYBA O, REEDER J, NAGARKAR DR, MODRUSAN Z, ALBERT ML, BYRD AL. Enrichment of oral-derived bacteria in inflamed colorectal tumors and distinct associations of Fusobacterium in the mesenchymal subtype[J]. Cell Reports Medicine, 2023, 4(2): 100920.
    [14] ABED J, EMGÅRD JEM, ZAMIR G, FAROJA M, ALMOGY G, GRENOV A, SOL A, NAOR R, PIKARSKY E, ATLAN KA, MELLUL A, CHAUSHU S, MANSON AL, EARL AM, OU N, BRENNAN CA, GARRETT WS, BACHRACH G. Fap2 mediates Fusobacterium nucleatum colorectal adenocarcinoma enrichment by binding to tumor-expressed gal-GalNAc[J]. Cell Host & Microbe, 2016, 20(2): 215-225.
    [15] ZHAO L, CHO WC, NICOLLS MR. Colorectal cancer-associated microbiome patterns and signatures[J]. Frontiers in Genetics, 2021, 12: 787176.
    [16] MOURADOV D, GREENFIELD P, LI S, IN EJ, STOREY C, SAKTHIANANDESWAREN A, GEORGESON P, BUCHANAN DD, WARD RL, HAWKINS NJ, SKINNER I, JONES IT, GIBBS P, MA CK, LIEW YJ, FUNG KYC, SIEBER OM. Oncomicrobial community profiling identifies clinicomolecular and prognostic subtypes of colorectal cancer[J]. Gastroenterology, 2023, 165(1): 104-120.
    [17] FLEMER B, LYNCH DB, BROWN JMR, JEFFERY IB, RYAN FJ, CLAESSON MJ, O’RIORDAIN M, SHANAHAN F, O’TOOLE PW. Tumour-associated and non-tumour-associated microbiota in colorectal cancer[J]. Gut, 2017, 66(4): 633-643.
    [18] LI YM, CAO H, FEI BJ, GAO QZ, YI WY, HAN WF, BAO CQ, XU JM, ZHAO W, ZHANG F. Gut microbiota signatures in tumor, para-cancerous, normal mucosa, and feces in colorectal cancer patients[J]. Frontiers in Cell and Developmental Biology, 2022, 10: 916961.
    [19] BAROT SV, SANGWAN N, NAIR KG, SCHMIT SL, XIANG S, KAMATH S, LISKA D, KHORANA AA. Distinct intratumoral microbiome of young-onset and average-onset colorectal cancer[J]. eBioMedicine, 2024, 100: 104980.
    [20] BURNS MB, LYNCH J, STARR TK, KNIGHTS D, BLEKHMAN R. Virulence genes are a signature of the microbiome in the colorectal tumor microenvironment[J]. Genome Medicine, 2015, 7(1): 55.
    [21] THOMAS AM, JESUS EC, LOPES A, AGUIAR S Jr, BEGNAMI MD, ROCHA RM, CARPINETTI PA, CAMARGO AA, HOFFMANN C, FREITAS HC, SILVA IT, NUNES DN, SETUBAL JC, DIAS-NETO E. Tissue-associated bacterial alterations in rectal carcinoma patients revealed by 16S rRNA community profiling[J]. Frontiers in Cellular and Infection Microbiology, 2016, 6: 179.
    [22] KOSUMI K, HAMADA T, KOH H, BOROWSKY J, BULLMAN S, TWOMBLY TS, NEVO D, MASUGI Y, LIU L, Da SILVA A, CHEN Y, DU CX, GU MC, LI CX, LI WW, LIU HL, SHI Y, MIMA K, SONG MY, NOSHO K, et al. The amount of Bifidobacterium genus in colorectal carcinoma tissue in relation to tumor characteristics and clinical outcome[J]. The American Journal of Pathology, 2018, 188(12): 2839-2852.
    [23] ZHU YB, MA L, WEI WT, LI X, CHANG YX, PAN ZY, GAO H, YANG RF, BI YJ, DING L. Metagenomics analysis of cultured mucosal bacteria from colorectal cancer and adjacent normal mucosal tissues[J]. Journal of Medical Microbiology, 2022. DOI: 10.1099/jmm.0.001523.
    [24] WANG X, JIA YQ, WEN LL, MU WX, WU XR, LIU T, LIU XQ, FANG J, LUAN YZ, CHEN P, GAO JL, NGUYEN KA, CUI J, ZENG GC, LAN P, CHEN QM, CHENG B, WANG Z. Porphyromonas gingivalis promotes colorectal carcinoma by activating the hematopoietic NLRP3 inflammasome[J]. Cancer Research, 2021, 81(10): 2745-2759.
    [25] LO CH, WU DC, JAO SW, WU CC, LIN CY, CHUANG CH, LIN YB, CHEN CH, CHEN YT, CHEN JH, HSIAO KH, CHEN YJ, CHEN YT, WANG JY, LI LH. Enrichment of Prevotella intermedia in human colorectal cancer and its additive effects with Fusobacterium nucleatum on the malignant transformation of colorectal adenomas[J]. Journal of Biomedical Science, 2022, 29(1): 88.
    [26] TSOI H, CHU ESH, ZHANG X, SHENG JQ, NAKATSU G, NG SC, CHAN AWH, CHAN FKL, SUNG JJY, YU J. Peptostreptococcus anaerobius induces intracellular cholesterol biosynthesis in colon cells to induce proliferation and causes dysplasia in mice[J]. Gastroenterology, 2017, 152(6): 1419-1433.e5.
    [27] BERGSTEN E, MESTIVIER D, DONNADIEU F, PEDRON T, BARAU C, MEDA LT, METTOUCHI A, LEMICHEZ E, GORGETTE O, CHAMAILLARD M, VAYSSE A, VOLANT S, DOUKANI A, SANSONETTI PJ, SOBHANI I, NIGRO G. Parvimonas micra, an oral pathobiont associated with colorectal cancer, epigenetically reprograms human colonocytes[J]. Gut Microbes, 2023, 15(2): 2265138.
    [28] OKUDA S, SHIMADA Y, TAJIMA Y, YUZA K, HIROSE Y, ICHIKAWA H, NAGAHASHI M, SAKATA J, LING YW, MIURA N, SUGAI MK, WATANABE Y, TAKEUCHI S, WAKAI T. Profiling of host genetic alterations and intra-tumor microbiomes in colorectal cancer[J]. Computational and Structural Biotechnology Journal, 2021, 19: 3330-3338.
    [29] ZHU YN, SHI T, LU X, XU Z, QU JX, ZHANG ZY, SHI GP, SHEN SN, HOU YY, CHEN YG, WANG TT. Fungal-induced glycolysis in macrophages promotes colon cancer by enhancing innate lymphoid cell secretion of IL-22[J]. The EMBO Journal, 2021, 40(11): e105320.
    [30] ZHANG XS, YU D, WU D, GAO XT, SHAO F, ZHAO M, WANG J, MA JW, WANG WZ, QIN XW, CHEN Y, XIA PY, WANG S. Tissue-resident Lachnospiraceae family bacteria protect against colorectal carcinogenesis by promoting tumor immune surveillance[J]. Cell Host & Microbe, 2023, 31(3): 418-432.e8.
    [31] LI GP, JIN Y, CHEN BL, LIN AQ, WANG EC, XU FH, HU GC, XIAO CX, LIU HL, HOU XH, ZHANG BZ, SONG J. Exploring the relationship between the gut mucosal virome and colorectal cancer: characteristics and correlations[J]. Cancers, 2023, 15(14): 3555.
    [32] ULERI E, PIU C, CAOCCI M, IBBA G, SANGES F, PIRA G, MURGIA L, BARMINA M, GIANNECCHINI S, PORCU A, SERRA C, SCANU AM, de MIGLIO MR, DOLEI A. Multiple signatures of the JC polyomavirus in paired normal and altered colorectal mucosa indicate a link with human colorectal cancer, but not with cancer progression[J]. International Journal of Molecular Sciences, 2019, 20(23): 5965.
    [33] NAGI K, GUPTA I, JURDI N, YASMEEN A, VRANIC S, BATIST G, AL MOUSTAFA AE. Copresence of high-risk human papillomaviruses and epstein-barr virus in colorectal cancer: a tissue microarray and molecular study from Lebanon[J]. International Journal of Molecular Sciences, 2021, 22(15): 8118.
    [34] REQUENA DO, GARCIA-BUITRAGO M. Molecular insights into colorectal carcinoma[J]. Archives of Medical Research, 2020, 51(8): 839-844.
    [35] LI XY, WU DF, LI QY, GU JL, GAO WX, ZHU XY, YIN WJ, ZHU RX, ZHU LX, JIAO N. Host-microbiota interactions contributing to the heterogeneous tumor microenvironment in colorectal cancer[J]. Physiological Genomics, 2024, 56(2): 221-234.
    [36] BYRD DA, FAN WY, GREATHOUSE KL, WU MC, XIE H, WANG XF. The intratumor microbiome is associated with microsatellite instability[J]. Journal of the National Cancer Institute, 2023, 115(8): 989-993.
    [37] LIU WX, ZHANG X, XU HZ, LI SM, LAU HCH, CHEN QY, ZHANG B, ZHAO LY, CHEN HR, SUNG JJY, YU J. Microbial community heterogeneity within colorectal neoplasia and its correlation with colorectal carcinogenesis[J]. Gastroenterology, 2021, 160(7): 2395-2408.
    [38] WU ZH, MA Q, GUO Y, YOU FM. The role of Fusobacterium nucleatum in colorectal cancer cell proliferation and migration[J]. Cancers, 2022, 14(21): 5350.
    [39] YAMAMOTO S, KINUGASA H, HIRAI M, TERASAWA H, YASUTOMI E, OKA S, OHMORI M, YAMASAKI Y, INOKUCHI T, HARADA K, HIRAOKA S, NOUSO K, TANAKA T, TERAISHI F, FUJIWARA T, OKADA H. Heterogeneous distribution of Fusobacterium nucleatum in the progression of colorectal cancer[J]. Journal of Gastroenterology and Hepatology, 2021, 36(7): 1869-1876.
    [40] KNEIS B, WIRTZ S, WEBER K, DENZ A, GITTLER M, GEPPERT C, BRUNNER M, KRAUTZ C, SIEBENHÜNER AR, SCHIERWAGEN R, TYC O, AGAIMY A, GRÜTZMANN R, TREBICKA J, KERSTING S, LANGHEINRICH M. Colon cancer microbiome landscaping: differences in right- and left-sided colon cancer and a tumor microbiome-ileal microbiome association[J]. International Journal of Molecular Sciences, 2023, 24(4): 3265.
    [41] ZHONG MY, XIONG YB, YE ZJ, ZHAO JB, ZHONG LF, LIU Y, ZHU YK, TIAN LT, QIU XF, HONG XH. Microbial community profiling distinguishes left-sided and right-sided colon cancer[J]. Frontiers in Cellular and Infection Microbiology, 2020, 10: 498502.
    [42] KOLISNIK T, SULIT AK, SCHMEIER S, FRIZELLE F, PURCELL R, SMITH A, SILANDER O. Identifying important microbial and genomic biomarkers for differentiating right- versus left-sided colorectal cancer using random forest models[J]. BMC Cancer, 2023, 23(1): 647.
    [43] NAKATSU G, LI XC, ZHOU HK, SHENG JQ, WONG SH, WU WKK, NG SC, TSOI H, DONG YJ, ZHANG N, HE YQ, KANG Q, CAO L, WANG KN, ZHANG JW, LIANG QY, YU J, SUNG JJY. Gut mucosal microbiome across stages of colorectal carcinogenesis[J]. Nature Communications, 2015, 6: 8727.
    [44] MURPHY CL, BARRETT M, PELLANDA P, KILLEEN S, McCOURT M, ANDREWS E, RIORDAIN MO, SHANAHAN F, O’TOOLE P. Mapping the colorectal tumor microbiota[J]. Gut Microbes, 2021, 13(1): 1-10.
    [45] BAKAR YÖ, DEMIRYAS S, KıLıNÇARSLAN AC, DEMIRCI M, KEPIL N, BAKAR MT, TANER Z, TOKUÇ E, ZIYAD MA, TAŞÇı İ, KOCAZEYBEK BS, TOKMAN HB. The relationship of enterotoxigenic Bacteroides fragilis and Fusobacterium nucleatum intestinal colonization with colorectal cancer: a case-control study performed with colon biopsies[J]. Mikrobiyoloji Bulteni, 2023, 57(3): 353-364.
    [46] XUE C, CHU QF, ZHENG QX, YUAN X, SU YS, BAO ZY, LU J, LI LJ. Current understanding of the intratumoral microbiome in various tumors[J]. Cell Reports Medicine, 2023, 4(1): 100884.
    [47] POORE GD, KOPYLOVA E, ZHU QY, CARPENTER C, FRARACCIO S, WANDRO S, KOSCIOLEK T, JANSSEN S, METCALF J, SONG SJ, KANBAR J, MILLER-MONTGOMERY S, HEATON R, MCKAY R, PATEL SP, SWAFFORD AD, KNIGHT R. Microbiome analyses of blood and tissues suggest cancerdiagnostic approach[J]. Nature, 2020, 579: 567-574.
    [48] ZHENG WS, ZHAO SJ, YIN YH, ZHANG HD, NEEDHAM DM, EVANS ED, DAI CL, LU PJ, ALM EJ, WEITZ DA. High-throughput, single-microbe genomics with strain resolution, applied to a human gut microbiome[J]. Science, 2022, 376(6597): eabm1483.
    [49] BULLMAN S. INVADEseq to study the intratumoural microbiota at host single-cell resolution[J]. Nature Reviews Cancer, 2023, 23: 189.
    [50] CAO YY, WANG ZH, YAN YQ, JI LH, HE J, XUAN BQ, SHEN CQ, MA YR, JIANG SS, MA D, TONG TY, ZHANG XY, GAO ZY, ZHU XQ, FANG JY, CHEN HY, HONG J. Enterotoxigenic bacteroidesfragilis promotes intestinal inflammation and malignancy by inhibiting exosome-packaged miR-149-3p[J]. Gastroenterology, 2021, 161(5): 1552-1566.e12.
    [51] ALLEN J, HAO S, SEARS CL, TIMP W. Epigenetic changes induced by Bacteroides fragilis toxin[J]. Infection and Immunity, 2019, 87(6): e00447-18.
    [52] PLEGUEZUELOS-MANZANO C, PUSCHHOF J, ROSENDAHL HUBER A, van HOECK A, WOOD HM, NOMBURG J, GURJAO C, MANDERS F, DALMASSO G, STEGE PB, PAGANELLI FL, GEURTS MH, BEUMER J, MIZUTANI T, MIAO Y, van der LINDEN R, van der ELST S, AMBROSE JC, ARUMUGAM P, BAPLE EL, BLEDA M, et al. Mutational signature in colorectal cancer caused by genotoxic pks+ E. coli[J]. Nature, 2020, 580: 269-273.
    [53] JOO JE, CHU YL, GEORGESON P, WALKER R, MAHMOOD K, CLENDENNING M, MEYERS AL, COMO J, JOSELAND S, PRESTON SG, DIEPENHORST N, TONER J, INGLE DJ, SHERRY NL, METZ A, LYNCH BM, MILNE RL, SOUTHEY MC, HOPPER JL, WIN AK, et al. Intratumoral presence of the genotoxic gut bacteria pks+ E. coli, Enterotoxigenic Bacteroides fragilis, and Fusobacterium nucleatum and their association with clinicopathological and molecular features of colorectal cancer[J]. British Journal of Cancer, 2024, 130(5): 728-740.
    [54] CHEN BJ, RAMAZZOTTI D, HEIDE T, SPITERI I, FERNANDEZ-MATEOS J, JAMES C, MAGNANI L, GRAHAM TA, SOTTORIVA A. Contribution of pks+ E. coli mutations to colorectal carcinogenesis[J]. Nature Communications, 2023, 14: 7827.
    [55] DEJEA CM, FATHI P, CRAIG JM, BOLEIJ A, TADDESE R, GEIS AL, WU XQ, DESTEFANO SHIELDS CE, HECHENBLEIKNER EM, HUSO DL, ANDERS RA, GIARDIELLO FM, WICK EC, WANG H, WU SG, PARDOLL DM, HOUSSEAU F, SEARS CL. Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria[J]. Science, 2018, 359(6375): 592-597.
    [56] ZHENG X, LIU R, ZHOU CC, YU HP, LUO WY, ZHU JH, LIU JX, ZHANG Z, XIE N, PENG X, XU X, CHENG L, YUAN Q, HUANG CH, ZHOU XD. ANGPTL4-mediated promotion of glycolysis facilitates the colonization of Fusobacterium nucleatum in colorectal cancer[J]. Cancer Research, 2021, 81(24): 6157-6170.
    [57] KONG C, YAN XB, ZHU YF, ZHU HY, LUO Y, LIU PP, FERRANDON S, KALADY MF, GAO RY, HE JD, YIN F, QU X, ZHENG JY, GAO YH, WEI Q, MA YL, LIU JY, QIN HL. Fusobacterium nucleatum promotes the development of colorectal cancer by activating a cytochrome P450/epoxyoctadecenoic acid axis via TLR4/Keap1/NRF2 signaling[J]. Cancer Research, 2021, 81(17): 4485-4498.
    [58] BELL HN, REBERNICK RJ, GOYERT J, SINGHAL R, KULJANIN M, KERK SA, HUANG W, DAS NK, ANDREN A, SOLANKI S, MILLER SL, TODD PK, FEARON ER, LYSSIOTIS CA, GYGI SP, MANCIAS JD, SHAH YM. Reuterin in the healthy gut microbiome suppresses colorectal cancer growth through altering redox balance[J]. Cancer Cell, 2022, 40(2): 185-200.e6.
    [59] GUO SH, PENG Y, LOU Y, CAO LJ, LIU JQ, LIN NM, CAI S, KANG Y, ZENG S, YU LS. Downregulation of the farnesoid X receptor promotes colorectal tumorigenesis by facilitating enterotoxigenic Bacteroides fragilis colonization[J]. Pharmacological Research, 2022, 177: 106101.
    [60] BAO YJ, TANG JY, QIAN Y, SUN TT, CHEN HM, CHEN ZF, SUN DF, ZHONG M, CHEN HY, HONG J, CHEN YX, FANG JY. Long noncoding RNA BFAL1 mediates enterotoxigenic Bacteroides fragilis-related carcinogenesis in colorectal cancer via the RHEB/mTOR pathway[J]. Cell Death & Disease, 2019, 10: 675.
    [61] GUERRA L, ALBIHN A, TRONNERSJÖ S, YAN QZ, GUIDI R, STENERLÖW B, STERZENBACH T, JOSENHANS C, FOX JG, SCHAUER DB, THELESTAM M, LARSSON LG, HENRIKSSON M, FRISAN T. Myc is required for activation of the ATM-dependent checkpoints in response to DNA damage[J]. PLoS One, 2010, 5(1): e8924.
    [62] O’DONNELL KA, WENTZEL EA, ZELLER KI, DANG CV, MENDELL JT. C-Myc-regulated microRNAs modulate E2F1 expression[J]. Nature, 2005, 435: 839-843.
    [63] HU SE, LIU L, CHANG EB, WANG JY, RAUFMAN JP. Butyrate inhibits pro-proliferative miR-92a by diminishing c-Myc-induced miR-17-92a cluster transcription in human colon cancer cells[J]. Molecular Cancer, 2015, 14: 180.
    [64] CHANG YX, HUANG ZR, HOU FY, LIU YJ, WANG LK, WANG Z, SUN YF, PAN ZY, TAN YF, DING L, GAO H, YANG RF, BI YJ. Parvimonas micra activates the Ras/ERK/c-Fos pathway by upregulating miR-218-5p to promote colorectal cancer progression[J]. Journal of Experimental & Clinical Cancer Research, 2023, 42(1): 13.
    [65] JIANG YF, HUANG YQ, HU YE, YANG Y, YOU FM, HU QY, LI XK, ZHAO ZY. Banxia Xiexin Decoction delays colitis-to-cancer transition by inhibiting E-cadherin/β-catenin pathway via Fusobacterium nucleatum FadA[J]. Journal of Ethnopharmacology, 2024, 328: 117932.
    [66] YU T, GUO FF, YU YN, SUN TT, MA D, HAN JX, QIAN Y, KRYCZEK I, SUN DF, NAGARSHETH N, CHEN YX, CHEN HY, HONG J, ZOU WP, FANG JY. Fusobacterium nucleatum promotes chemoresistance to colorectal cancer by modulating autophagy[J]. Cell, 2017, 170(3): 548-563.e16.
    [67] TANG B, LU XX, TONG YN, FENG YY, MAO YL, DUN GD, LI J, XU QL, TANG J, ZHANG T, DENG L, HE XY, LAN YZ, LUO HX, ZENG LH, XIANG YY, LI Q, ZENG DZ, MAO XH. MicroRNA-31 induced by Fusobacterium nucleatum infection promotes colorectal cancer tumorigenesis[J]. iScience, 2023, 26(5): 106770.
    [68] QU X, YIN F, PEI MM, CHEN Q, ZHANG YY, LU SW, ZHANG XL, LIU ZY, LI XY, CHEN HR, ZHANG Y, QIN HL. Modulation of intratumoral Fusobacterium nucleatum to enhance sonodynamic therapy for colorectal cancer with reduced phototoxic skin injury[J]. ACS Nano, 2023, 17(12): 11466-11480.
    [69] MISHRA A, BHARTI PS, RANI N, NIKOLAJEFF F, KUMAR S. A tale of exosomes and their implication in cancer[J]. Biochimica et Biophysica Acta Reviews on Cancer, 2023, 1878(4): 188908.
    [70] ZHANG MJ, WANG YF, YU LC, ZHANG YL, WANG YL, SHANG ZQ, XIN YW, LI XY, NING NN, ZHANG Y, ZHANG X. Fusobacterium nucleatum promotes colorectal cancer metastasis by excretion of miR-122-5p from cells via exosomes[J]. iScience, 2023, 26(9): 107686.
    [71] GUO SH, CHEN J, CHEN FF, ZENG QY, LIU WL, ZHANG G. Exosomes derived from Fusobacterium nucleatum-infected colorectal cancer cells facilitate tumour metastasis by selectively carrying miR-1246/92b-3p/27a-3p and CXCL16[J]. Gut, 2020: gutjnl-2020-321187.
    [72] BULLMAN S, PEDAMALLU CS, SICINSKA E, CLANCY TE, ZHANG XY, CAI DA, NEUBERG D, HUANG K, GUEVARA F, NELSON T, CHIPASHVILI O, HAGAN T, WALKER M, RAMACHANDRAN A, DIOSDADO B, SERNA G, MULET N, LANDOLFI S, CAJAL SRY, FASANI R, et al. Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer[J]. Science, 2017, 358(6369): 1443-1448.
    [73] ZHANG Y, ZHANG L, ZHENG S, LI MJ, XU CC, JIA D, QI YD, HOU TY, WANG L, WANG BY, LI AQ, CHEN SJ, SI JM, ZHUO W. Fusobacterium nucleatum promotes colorectal cancer cells adhesion to endothelial cells and facilitates extravasation and metastasis by inducing ALPK1/NF-κB/ICAM1 axis[J]. Gut Microbes, 2022, 14(1): 2038852.
    [74] YANG YZ, WENG WH, PENG JJ, HONG LM, YANG L, TOIYAMA Y, GAO RY, LIU MF, YIN MM, PAN C, LI H, GUO BM, ZHU QC, WEI Q, MOYER MP, WANG P, CAI SJ, GOEL A, QIN HL, MA YL. Fusobacterium nucleatum increases proliferation of colorectal cancer cells and tumor development in mice by activating toll-like receptor 4 signaling to nuclear factor-κB, and up-regulating expression of microRNA-21[J]. Gastroenterology, 2017, 152(4): 851-866.e24.
    [75] KORDAHI MC, STANAWAY IB, AVRIL M, CHAC D, BLANC MP, ROSS B, DIENER C, JAIN S, McCLEARY P, PARKER A, FRIEDMAN V, HUANG J, BURKE W, GIBBONS SM, WILLIS AD, DARVEAU RP, GRADY WM, KO CW, DePAOLO RW. Genomic and functional characterization of a mucosal symbiont involved in early-stage colorectal cancer[J]. Cell Host & Microbe, 2021, 29(10): 1589-1598.e6.
    [76] CAVALLUCCI V, PALUCCI I, FIDALEO M, MERCURI A, MASI L, EMOLI V, BIANCHETTI G, FIORI ME, BACHRACH G, SCALDAFERRI F, MAULUCCI G, DELOGU G, PANI G. Proinflammatory and cancer-promoting pathobiont Fusobacterium nucleatum directly targets colorectal cancer stem cells[J]. Biomolecules, 2022, 12(9): 1256.
    [77] LONG XH, WONG CC, TONG L, CHU ESH, HO SZETO C, GO MYY, COKER OO, CHAN AWH, CHAN FKL, SUNG JJY, YU J. Peptostreptococcus anaerobius promotes colorectal carcinogenesis and modulates tumour immunity[J]. Nature Microbiology, 2019, 4: 2319-2330.
    [78] RALSER A, DIETL A, JAROSCH S, ENGELSBERGER V, WANISCH A, JANSSEN KP, MIDDELHOFF M, VIETH M, QUANTE M, HALLER D, BUSCH DH, DENG L, MEJÍAS-LUQUE R, GERHARD M. Helicobacter pylori promotes colorectal carcinogenesis by deregulating intestinal immunity and inducing a mucus-degrading microbiota signature[J]. Gut, 2023, 72(7): 1258-1270.
    [79] ABDULAMIR AS, HAFIDH RR, ABU BAKAR F. Molecular detection, quantification, and isolation of Streptococcus gallolyticus bacteria colonizing colorectal tumors: inflammation-driven potential of carcinogenesis via IL-1, COX-2, and IL-8[J]. Molecular Cancer, 2010, 9: 249.
    [80] LIU Z, ZHANG XM, ZHANG HD, ZHANG H, YI ZY, ZHANG QQ, LIU QS, LIU XY. Multi-omics analysis reveals intratumor microbes as immunomodulators in colorectal cancer[J]. Microbiology Spectrum, 2023, 11(2): e0503822.
    [81] HILMI M, KAMAL M, VACHER S, DUPAIN C, IBADIOUNE S, HALLADJIAN M, SABLIN MP, MARRET G, AJGAL ZC, NIJNIKOFF M, SALOMON A, EL BEAINO Z, SERVANT N, DUREAU S, SOKOL H, NICOLLE R, Le TOURNEAU C, BIECHE I, NEUZILLET C. Intratumoral microbiome is driven by metastatic site and associated with immune histopathological parameters: an ancillary study of the SHIVA clinical trial[J]. European Journal of Cancer, 2023, 183: 152-161.
    [82] BOROWSKY J, HARUKI K, LAU MC, COSTA AD, VÄYRYNEN JP, UGAI T, ARIMA K, Da SILVA A, FELT KD, ZHAO M, GURJAO C, TWOMBLY TS, FUJIYOSHI K, VÄYRYNEN SA, HAMADA T, MIMA K, BULLMAN S, HARRISON TA, PHIPPS AI, PETERS U, et al. Association of Fusobacterium nucleatum with specific T-cell subsets in the colorectal carcinoma microenvironment[J]. Clinical Cancer Research, 2021, 27(10): 2816-2826.
    [83] Colonic microbiota promote antitumor immunity in colorectal cancer[J]. Cancer Discovery, 2022, 12(2): 285.
    [84] SHI YY, ZHENG WX, YANG KT, HARRIS KG, NI KY, XUE L, LIN WB, CHANG EB, WEICHSELBAUM RR, FU YX. Intratumoral accumulation of gut microbiota facilitates CD47-based immunotherapy via STING signaling[J]. The Journal of Experimental Medicine, 2020, 217(5): e20192282.
    [85] CHEN Y, McANDREWS KM, KALLURI R. Clinical and therapeutic relevance of cancer-associated fibroblasts[J]. Nature Reviews Clinical Oncology, 2021, 18: 792-804.
    [86] CHEN SJ, FAN LN, LIN YF, QI YD, XU CC, GE QW, ZHANG Y, WANG QW, JIA D, WANG L, SI JM, WANG LJ. Bifidobacterium adolescentis orchestrates CD143+ cancer-associated fibroblasts to suppress colorectal tumorigenesis by Wnt signaling-regulated GAS1[J]. Cancer Communications, 2023, 43(9): 1027-1047.
    [87] PUSCHHOF J, PLEGUEZUELOS-MANZANO C, CLEVERS H. Organoids and organs-on-chips: insights into human gut-microbe interactions[J]. Cell Host & Microbe, 2021, 29(6): 867-878.
    [88] PUSCHHOF J, PLEGUEZUELOS-MANZANO C, MARTINEZ-SILGADO A, AKKERMAN N, SAFTIEN A, BOOT C, de WAAL A, BEUMER J, DUTTA D, HEO I, CLEVERS H. Intestinal organoid cocultures with microbes[J]. Nature Protocols, 2021, 16: 4633-4649.
    [89] FU AK, YAO BQ, DONG TT, CHEN YY, YAO J, LIU Y, LI H, BAI HR, LIU XQ, ZHANG Y, WANG CH, GUO YJ, LI N, CAI S. Tumor-resident intracellular microbiota promotes metastatic colonization in breast cancer[J]. Cell, 2022, 185(8): 1356-1372.e26.
    [90] YAN XJ, XIN YT, YU YJ, LI XH, LI BQ, ELSABAHY M, ZHANG JM, MA FH, GAO H. Remotely controllable supramolecular nanomedicine for drug-resistant colorectal cancer therapy caused by Fusobacterium nucleatum[J]. Small Methods, 2024, 8(3): e2301309.
    [91] GANESAN K, GUO SH, FAYYAZ S, ZHANG G, XU BJ. Targeting programmed Fusobacterium nucleatum Fap2 for colorectal cancer therapy[J]. Cancers, 2019, 11(10): 1592.
    [92] CHEN LF, ZHAO R, KANG ZY, CAO ZQ, LIU NH, SHEN JJ, WANG C, PAN F, ZHOU X, LIU Z, YANG Y, CHEN Q. Delivery of short chain fatty acid butyrate to overcome Fusobacterium nucleatum-induced chemoresistance[J]. Journal of Controlled Release, 2023, 363: 43-56.
    [93] LI XH, NIU JZ, DENG LL, YU YJ, ZHANG LW, CHEN QX, ZHAO JW, WANG BM, GAO H. Amphiphilic polymeric nanodrug integrated with superparamagnetic iron oxide nanoparticles for synergistic antibacterial and antitumor therapy of colorectal cancer[J]. Acta Biomaterialia, 2024, 173: 432-441.
    [94] ZHANG J, HASTY J, ZARRINPAR A. Live bacterial therapeutics for detection and treatment of colorectal cancer[J]. Nature Reviews Gastroenterology & Hepatology, 2024, 21: 295-296.
    [95] CHEN LF, ZHAO R, SHEN JJ, LIU NH, ZHENG ZX, MIAO Y, ZHU JF, ZHANG L, WANG YY, FANG HP, ZHOU J, LI MY, YANG Y, LIU Z, CHEN Q. Antibacterial Fusobacterium nucleatum-mimicking nanomedicine to selectively eliminate tumor-colonized bacteria and enhance immunotherapy against colorectal cancer[J]. Advanced Materials, 2023, 35(45): e2306281.
    Cited by
    Comments
    Comments
    分享到微博
    Submit
Get Citation

LONG Jing, WANG Qian, JIANG Yifang, LUO Yuanke, XIAO Chong, YOU Fengming, LI Xueke. Current status and prospects of research on intratumoral microorganisms and progression of colorectal cancer[J]. Microbiology China, 2025, 52(1): 60-77

Copy
Share
Article Metrics
  • Abstract:100
  • PDF: 194
  • HTML: 158
  • Cited by: 0
History
  • Received:April 17,2024
  • Adopted:May 28,2024
  • Online: January 21,2025
  • Published: January 20,2025
Article QR Code
  • WeChat ID
  • Mobile Terminal

Microbiology China ® 2025 All Rights Reserved